Though we were able to shorten the CD34+ cell mobilization by 24~48h by using continuous intravenous rhG-CSF rather than SQ rhG-CSF, it still will take several days when used normal individuals (

Lee et al, BMT 2005, 36:1027–1031
). Previously we had reported that LT(Leukotriene)B4 was able to mobilize HSC in the murine model within 4 hours without significant side effects(ASH 2005). However, because there are possibilities of similar mechanisms during the HSC mobilization, which are shared by rhG-CSF or LTB4, in this study, we investigated the role of LTB4 receptors by rhG-CSF during HSC mobilization. LTB4APA and U75302, which are LTB4 receptor antagonists were given to C57BL/6 mice at different dose levels(0.5μg, 1μg, 2μg or PBS with equal volume in control arm) followed by rhG-CSF(5μg, IV) 2 hours later. 24 hours after the rhG-CSF injection, peripheral blood samples were obtained via cardiac puncture. The samples were analyzed for TNC using a trypan blue stain and FACS analysis were performed using Sca-1, Lin, CD45R(B220), CD116, Gr-1, TER119. The number of WBC and HSC were decreased in the rhG-CSF mobilized mice, in which LTB4 receptor antagonists were given. In those with up to 1μg of LTB4APA or U75302, there were tendencies of the blocking of the mobilization in the dose dependent manner. However, beyond 1μg of LTB4 receptor antagonists, the blocking effects plateaued. Interestingly, the blocking effects on mobilization by LTB4 receptor antagonists were more dramatic by the rh-GCSF than by the LTB4. Through our data, one can conclude that the LTB4 receptor is involved not only in the downstream pathway of rh-GCSF mobilization, but in the LTB4 mobilization pathway in C57BL/6 mice. Currently, hematopoietic stem cells mobilization is being tested to see the effects of rh-GCSF on LTB4 K/O mice. It is necessary to have insight into understandings more precise mechanisms on rhG-CSF and LTB4 mobilization for developing efficient protocols in the clinic.

Topics:
granulocyte colony-stimulating factor, leukotriene b4, leukotriene b4 receptors, mice, mice, inbred c57bl, colony-stimulating factors, antagonists, adverse effects, leukotrienes, painful bladder syndrome

Disclosures: Korea Research Foundation.

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2006, The American Society of Hematology
2006
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